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Large-scale profiling of protein palmitoylation in mammalian cells


S-palmitoylation is a pervasive post-translational modification required for the trafficking, compartmentalization and membrane tethering of many proteins. We demonstrate that the commercially available compound 17-octadecynoic acid (17-ODYA) can serve as a bioorthogonal, click chemistry probe for in situ labeling, identification and verification of palmitoylated proteins in human cells. We identified 125 predicted palmitoylated proteins, including G proteins, receptors and a family of uncharacterized hydrolases whose plasma membrane localization depends on palmitoylation.

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Figure 1: The 17-ODYA labeling and detection of palmitoylated proteins.
Figure 2: Membrane tethering of the FAM108 family of serine hydrolases by palmitoylation of an N-terminal cysteine-rich motif.


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We thank E. Weerapana (The Scripps Research Institute) for providing reagents and assistance with click chemistry and mass spectrometry, G. Simon for assistance with data analysis, W. Kiossis for microscopy instruction and members of the Cravatt laboratory for helpful discussions. This research was funded by F32NS060559, CA087660 and the Skaggs Institute for Chemical Biology.

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B.R.M. performed experiments. B.R.M. and B.F.C. designed experiments, analyzed data and wrote the paper.

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Correspondence to Benjamin F Cravatt.

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Martin, B., Cravatt, B. Large-scale profiling of protein palmitoylation in mammalian cells. Nat Methods 6, 135–138 (2009).

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